The research objectives of this proposal are to study very broadly all phases of the regulation of aldosterone secretion, its distribution and metabolism, and its action on the nephron to stimulate sodium and fluid reabsorption. To accomplish these goals, we will use control system block analyses and computer solutions coupled with animal experimentation to provide the quantitative data necessary to express in mathematical terms the relative importance and interrelationsip of the mehcanisms which control aldosterone secretion under normal conditions and during states of circulatory stress such as congestive heart failure, hypertension, shock, edema, and so forth. Using propranolol to inhibit renin secretion, angiotensin II inhibitory analogues to block angiotensin II at receptor sites in the vascular smooth muscle and in the adrenal cortex, and angiotensin I converting enzyme inhibitors to block formation of angiotensin II, we plan to evaluate the role of the renin-angiotensin system in the control of aldosterone secretion and arterial blood pressure during sodium deficiency. Using the new potent, orally-active angiotensin I converting enzyme inhibitor, SQ-14,225, we propose to define the role of the renin-angiotensin system in the maintenance of aldosterone secretion and arterial blood pressure in established renal hypertension. In order to define the interrelationship of aldosterone and the kallikrein-kinin system, we propose to (a) determine whether increased kallikrein-kinin activity is responsible for the aldosterone "escape mechanism" and to determine whether failure to escape by animals with congestive heart failure results from failure of the renal kallikrein-kinin system to become activated, and (b) determine whether kallikrein is directly induced or activated by aldosterone and to more clearly define its intrarenal action.